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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)
 
 
 

Activation of inhibition from the periaqueductal grey matter mediates central analgesic effect of metamizol (dipyrone).

The pyrazolone derivative, metamizol (dipyrone), possesses analgesic, antipyretic, anti-inflammatory and spasmolytic properties. It is often classified as peripherally acting. To test the possibility that a central action of the drug contributes to its antinociceptive and analgesic effects, experiments were carried out in which the tail-flick response to radiant heat, flexor reflex activity in the tibialis anterior muscle and activity in ascending spinal axons evoked by stimulation of afferent C fibres in the sural nerve, and activity of neurones in the periaqueductal grey matter and the substantia nigra were assessed in rats. Metamizol administered by intraperitoneal (i.p.; 10, 20 and 40 mg/kg) or intrathecal (i.t.; 50 to 400 micrograms) injection to intact rats dose-dependently prolonged the tail-flick latency. Administration by i.t. injection to spinal rats was without effect. Intravenous (i.v.) injection of metamizol (140 mg/kg) reduced flexor reflex activity in intact animals, while an i.t. injection to spinal rats was ineffective at a low dose (100 micrograms) or enhanced the reflex activity at a higher dose (400 micrograms). Activity in ascending axons responding to afferent C fibre stimulation was mostly depressed by i.t. injection of metamizol (40, 80 and 140 mg/kg) in rats with an intact spinal cord. Ascending activity was increased by i.t. injection of the drug (100 and 200 micrograms) to spinal rats. Metamizol (140 mg/kg) i.v. increased the activity of neurones in the PAG and reduced that of neurones in the substantia nigra. Metamizol administered by microinjection into the PAG prolonged the tail-flick latency (15-100 micrograms) and depressed C fibre-evoked activity in ascending axons (100 micrograms). The results suggest that a central action is involved in the analgesic effect of metamizol and that this central action manifests itself by an activation of inhibition originating in the PAG.[1]

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